Text written by Nóra Lehotai and Magnus Ölander. Picture credits go to Magnus Ölander.
This episode of the MIMS Spotlight Series is part of "MIMS highlights World Antimicrobial Awareness Week 2021" article series. Magnus has Swedish nationality, lives with his wife and two sons in Umeå, has lived only in Sweden so far and he joined MIMS in October 2019 to work with MIMS group leader Barbara Sixt.
Can you tell us about your role at MIMS, what are you working on now?
I have been a postdoc in the Sixt lab for a couple of years now. I am working on a drug discovery project to find new compounds that can combat infection by Chlamydia trachomatis. Chlamydia trachomatis is an obligate intracellular bacterium affecting a lot of people, resulting in more than 100 million cases per year globally. It is very common in Sweden as well, especially among young people since it causes a sexually transmitted disease (STD). It can be quite easily treated, but usually with broad-spectrum antibiotics. These antibiotics kill everything in an uncontrollable way, meaning that they wipe out the normal microbiota in our intestine. The microbiota recovers after a while, but it doesn't necessarily grow back in the same way it was before. We also don't really know the downstream effects of harming the microbiota. Another problem is that antibiotic treatment against C. trachomatis can increase the pressure for resistance development in other pathogenic bacteria that happen to be present.
Through screening, we have this set of highly potent compounds that we discovered and now, in the second half of my project, we want to try to figure out how they work, their mode of action. I really enjoy that this project allows me to develop my skills in machine learning. We have combined the data from our big compound screen with data from the literature on other compounds that people have tried against C. trachomatis and used molecular properties derived from chemical structures to develop machine-learning-based predictive models. We can then put an unknown structure into the model and the model will tell us whether it is likely to be anti-chlamydial or not. We recently screened an online database of millions of compounds, and then used the output of that to select just a small number of compounds for experimental testing. The early results look quite promising, which is super cool since we could never screen that many compounds in the lab.
What were you doing before you joined MIMS and what attracted you to start a position here?
This is my first postdoc. I came here directly after finishing my PhD in pharmaceutical sciences at Uppsala University. My PhD project was about how the human liver and small intestine take up and process drugs. Before that, I was actually working for a couple of years at a small antibiotic development company here in Umeå, called Creative Antibiotics, a start-up company assisted by Umeå Biotech Incubator. Unfortunately, they lost funding in summer 2013 and that is when I started my PhD. I did my master’s at Umeå University, in biotechnology with a medical profile. I was interested in antibiotics since then and when I saw the ad for this project in Barbara’s group at MIMS, I thought that it was a cool combination of my previous interest of antibiotic development plus the sort of know-how about drug development and discovery that I got during my PhD. I thought that it was a very nice opportunity and since I have lived here before in Umeå, it was fun to come back.
If you would not have your current profession, what do you think you would be doing?
When I was a kid, I dreamt of being an archaeologist or a paleontologist. That interest has stayed with me ever since, so I think I would spend my time digging in the ground for old bones.
What do you do in your free time and what are you most enjoying in living in Umeå, Sweden?
I have two small kids and they are most of my free time until they fall asleep. I love hanging out with them, they are super fun. When I don't hang out with the kids, I enjoy playing video games and reading science fiction and fantasy. I tried to get my wife into playing games together but so far, she is not that enthusiastic. I come from even further up north than Umeå and southerners and foreigners often have this expectation that you should be doing a lot of skiing, snow mobiles, hunting, and so on, but while growing up, these were not so integrated into my life so I am not the super outdoorsy type of person. I like biking, though, as well as hiking in the forest.
Two things Magnus enjoys: baking sourdough bread and cheering for his favourite hockey team from Luleå.
Is there a little known/interesting fact about yourself?
Well, something that I really enjoy is to make things you can eat that take a really long time to prepare, like slow cooked stews, sourdough bread and I recently got into beer making. I have different hops and malts but I haven't experimented so much with different yeasts yet. It is surprising how good it becomes! I enjoy following the long process for weeks, seeing it bubble here and there. The wheat sourdough I have has been alive since 2012. At some point, I would like to try to make cider and different types of beers because so far, I have made only ale.
World Antimicrobial Awarenes Week 2021
What does it mean to you: antimicrobial awareness?
In a societal sense, it is important for people to be aware that excessive use of antibiotics can cause the emergence of resistant strains of pathogenic bacteria. This can become a quite serious problem, not being able to treat infections anymore, returning us to a sort of pre-antibiotic era. People need to keep this in mind and not request antibiotics when it is not absolutely necessary and not to pressure healthcare providers to give them antibiotics.
What do you think about antibiotic use in the general public?
I know that Sweden and other Nordic countries are among the most restrictive in the prescription of antibiotics globally. I think that it is very good that we can lead in this way. Probably it is being increasingly recognised in other countries as well as the problem develops and hopefully people understand the basic difference between bacteria and viruses. Also, pharmacies should stop offering over-the-counter antibiotics everywhere.
How does this topic connect to your research?
It connects quite directly because we are trying to find new antimicrobials for a not very dangerous but very prevalent pathogen, which could decrease the use of broad-spectrum antibiotics and therefore reduce the risk of bacteria becoming resistant. Clinical resistance for Chlamydia trachomatis has not been described yet but it could arise in the future because it is relatively easy to get resistant bacteria in the lab by keeping the bacteria with sub-inhibitory concentrations of the antibiotics. Plus, there is the risk of resistant gene transfer between species while in the microbiota, for example.
What should be changed in the society to avoid rising antibiotic resistance?
I think of information campaigns but maybe it depends on which country we are talking about. My feeling is that here it is relatively well-known that we shouldn't take too much antibiotics nowadays but another problem is the prophylactic use of antibiotics in agriculture and animal husbandry. I think this represents a large portion of antibiotic use, which could promote resistance. This field of antibiotic use should be addressed and changed but I don’t exactly know how. This is not something you can solve in one day.
Awareness could perhaps be raised about the fact that antibiotic resistance is a problem already today, and not only in the future. The number of new antibiotic classes that appear over time has drastically decreased and “new” antibiotics are often new iterations of older, already existing types. Since pharmaceutical companies are not so interested in developing new antibiotics as it is not very profitable (we usually need only a few doses and not months/lifelong treatment), there may be a need for large-scale funding programmes from society.
A history lesson
Historically, a lot of the antibiotics we have, have been found in soil bacteria and other natural sources since in the environment, where is a constant war between different organisms trying to make the situation favourable for themselves, forcing other organisms to develop resistance against the compounds the enemy uses as weapon. People therefore mined different fungi and bacteria for new antimicrobials. Nowadays, we rely more on high-throughput screening approaches where large libraries of synthetic molecules can be rapidly tested. This often results in biologically interesting compounds, but the problems come in later stages of development as these compounds often have problems with solubility and bioavailability. The road from in vitro activity to actually working in the human body is quite long.
How does your research connect to the fight against rising antimicrobial resistance?
If we, in the end, are able to make a sort of narrow-spectrum antibiotic that is more specific for Chlamydia infections, we would not need to apply broad-spectrum antibiotics as much, thus decreasing the risk of antibiotic resistance arising. Another potential use for our compounds could be to apply them in combination therapy with existing antibiotics, which could enable lower dosing.
Picture credits: World Antimicrobial Awareness Week 2021 illustration "Go Blue" by WHO, Antibiotics by Mostphotos.